Introduction: We assessed whether modest systemic cooling started within 6 hours of symptom onset improves functional outcome at three months in awake patients with acute ischaemic stroke. Patients and methods: In this European randomised open-label clinical trial with blinded outcome assessment, adult patients with acute ischaemic stroke were randomised to cooling to a target body temperature of 34.0-35.0 C, started within 6 h after stroke onset and maintained for 12 or 24 h , versus standard treatment. The primary outcome was the score on the modified Rankin Scale at 91 days, as analysed with ordinal logistic regression. Results: The trial was stopped after inclusion of 98 of the originally intended 1500 patients because of slow recruitment and cessation of funding. Forty-nine patients were randomised to hypothermia versus 49 to standard treatment.

No abstract

Background: Renal impairment is a potent risk factor for stroke, which remains a leading cause of death and disability. Thrombolysis for acute ischemic stroke has transformed patient outcomes, although the safety and efficacy of this approach remain poorly characterized in patients with renal dysfunction, who manifest a higher risk of bleeding due to uremia. We therefore examined the impact of renal impairment on clinical outcomes with thrombolysis within the current 4.5-hour therapeutic window. Methods: This retrospective multicenter cohort study (2009–2011) examined 229 stroke patients receiving thrombolysis with alteplase (0.9 mg/kg; mean age 70 ± 13 years; 59% male, 24% diabetic). Sixty-five patients had an estimated glomerular filtration rate (eGFR) <60 ml/min. The primary outcome was the improvement in National Institutes of Health Stroke Scale (NIHSS) score at 24 h. Secondary outcomes included the NIHSS score at 7 days, the incidence of symptomatic and asymptomatic intracranial hemorrhage (ICH), extracranial bleeding and death during the index hospitalization. Univariate and multivariate regression analyses were performed to determine the association between demographic characteristics and comorbid factors of interest and outcomes. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Results: There was no significant difference in mean time to thrombolysis between the groups (221 ± 66 vs. 220 ± 70 min from symptom onset; p = 0.9). An eGFR <60 ml/min was independently associated with a statistically significant reduction of the therapeutic effect of alteplase at 24 h on multivariate regression [coefficient –2.3, 95% confidence interval (CI) –3.7 to –0.9; p = 0.002], and this persisted at 7 days (coefficient –3.5, 95% CI –5.3 to –1.7; p < 0.001). On modeling eGFR as a continuous variable, every 10 ml/min decline in eGFR was associated with a 0.40 diminution in NIHSS score improvement with alteplase (95% CI 0.07–0.74; p = 0.02). Older age and a higher presenting NIHSS score were associated with a greater therapeutic effect (p = 0.04 and p < 0.001, respectively). In-patient mortality was 5%, with no significant differences between groups. Renal impairment was not associated with a higher rate of ICH (6.2 vs. 6.7%; p = 0.9). Greater NIHSS score at presentation was the only factor associated with a greater risk of death (odds ratio 1.24, 95% CI 1.10–1.40; p < 0.001) and ICH (odds ratio 1.12, 95% CI 1.03–1.23; p = 0.004). Conclusions: Our results suggest that renal impairment is associated with reduced efficacy of thrombolysis in acute ischemic stroke without any excess hemorrhagic complications. This may relate to diminished fibrinolysis in the uremic milieu or differences in infarct anatomy. Longer-term prospective studies are required to characterize and improve functional outcomes following stroke in a manifestly high-risk group.

IMPORTANCE Cryptogenic strokes constitute approximately 40% of ischemic strokes in young adults, and most meet criteria for the embolic stroke of undetermined source (ESUS). Two randomized clinical trials, NAVIGATE ESUS and RESPECT ESUS, showed a high rate of stroke recurrence in older adults with ESUS but the prognosis and prognostic factors among younger individuals with ESUS is uncertain. OBJECTIVE To determine rates of and factors associated with recurrent ischemic stroke and death and new-onset atrial fibrillation (AF) among young adults. DESIGN, SETTING, AND PARTICIPANTSThis multicenter longitudinal cohort study with enrollment from October 2017 to October 2019 and a mean follow-up period of 12 months ending in October 2020 included 41 stroke research centers in 13 countries. Consecutive patients 50 years and younger with a diagnosis of ESUS were included. Of 576 screened, 535 participants were enrolled after 1 withdrew consent, 41 were found to be ineligible, and 2 were excluded for other reasons. The final follow-up visit was completed by 520 patients. MAIN OUTCOMES AND MEASURESRecurrent ischemic stroke and/or death, recurrent ischemic stroke, and prevalence of patent foramen ovale (PFO). RESULTSThe mean (SD) age of participants was 40.4 (7.3) years, and 297 (56%) participants were male. The most frequent vascular risk factors were tobacco use (240 patients [45%]), hypertension (118 patients [22%]), and dyslipidemia (109 patients [20%]). PFO was detected in 177 participants (50%) who had transthoracic echocardiograms with bubble studies. Following initial ESUS, 468 participants (88%) were receiving antiplatelet therapy, and 52 (10%) received anticoagulation. The recurrent ischemic stroke and death rate was 2.19 per 100 patient-years, and the ischemic stroke recurrence rate was 1.9 per 100 patient-years. Of the recurrent strokes, 9 (64%) were ESUS, 2 (14%) were cardioembolic, and 3 (21%) were of other determined cause. AF was detected in 15 participants (2.8%; 95% CI, 1.6-4.6). In multivariate analysis, the following were associated with recurrent ischemic stroke: history of stroke or transient ischemic attack (hazard ratio, 5.3; 95% CI,, presence of diabetes (hazard ratio, 4.4; 95% CI, 1.5-13), and history of coronary artery disease (hazard ratio, 10; 95% CI,. CONCLUSIONS AND RELEVANCEIn this large cohort of young adult patients with ESUS, there was a relatively low rate of subsequent ischemic stroke and a low frequency of new-onset AF. Most recurrent strokes also met the criteria for ESUS, suggesting the need for future studies to improve our understanding of the underlying stroke mechanism in this population.

Northwick Park Hospital in London, United Kingdom (UK) is one of the busiest stroke units in the country and is located in one of the areas most heavily affected by the COVID-19 pandemic in the first half of 2020. Admissions to the stroke unit and changes during the peak of COVID-19 were reviewed. Compared with the previous year, mean 96 patients were admitted with suspected stroke during April and May 2020 compared with mean 116 per month in non-COVID periods, ratio 0.82, P = 0.01. This reduction involved both strokes and mimics and was unlikely to have occurred by chance. Numbers of patients thrombolysed and of patients referred for thrombectomy decreased dramatically during this time. Mechanisms by which the COVID-19 pandemic and the March lockdown may have affected admissions to the unit are discussed. Reduced admissions to the stroke unit allowed it to contribute its resources to the care of patients with COVID-19 during the peak of admissions.